IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
MageB2 enhances rDNA transcription and global protein synthesis
Autor/es:
PASCUCCI FA; AMATO GE; LADELFA, M FÁTIMA; MONTE, MARTÍN
Reunión:
Congreso; LXIII Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC).; 2018
Institución organizadora:
Sociedad Argentina de Investigaciones Clínicas
Resumen:
MageB2 is a pro-proliferative and tumor specific protein belonging to MAGE family. Previously, we observed a reduced expression of MageB2 caused a reduction in the level of ribosomal RNA precursor (pre-rRNA). Here, we study the mechanisms involved in the regulation of ribosomal biogenesis by MageB2 as well as the effect on protein synthesis.The regulation of rDNA transcription is achieved via growth factor-dependent signaling pathways (mainly PI3K/AKT/mTOR and RAS/MEK/ERK) modulating the activities of Pol I-specific transcription factors, such as upstream binding factor (UBF). UBF phosphorylation enhances its association with Pol I and pre-rRNA synthesis.By using specific inhibitors of PI3K/AKT/mTOR and RAS/MEK/ERK pathways we observed the negative effect on UBF phosphorylation is contrarested when MageB2 is expressed. According to this, by performing Chromatin Immunoprecipitation assays we observed a reduced amount of pUBF is recruited to rDNA promoter in the HCT116 MageB2 KO in comparison with parental cell line. Next, we performed a proteomic study to identify proteins differentially expressed in HCT116 and HCT116 MageB2 KO cells. Notably, more than 35 ribosomal proteins were identified with reduced levels in MageB2 KO cells, supporting the idea that MageB2 is involved in ribosome biogenesis. In this way, abolition of MageB2 expression could lead to less ribosome production and therefore less content in ribosomal proteins. Finally, we used the non-isotopic SUnSET technique to measure protein synthesis. According to a reduced number of ribosomes, we observed a 30% reduction of global protein synthesis in the HCT116 MageB2 KO, which is reverted by ectopically expressing MageB2 in this cell line.Together, these results suggest a mechanism whereby MageB2 through its ability to upregulate phosphorylation of UBF, Pol I transcription and consequently, ribosomal biogenesis is able to affect global protein synthesis, collaborating in this way to the elevated proliferation rates required by cancer cells.